Transforming growth factor-beta 1 enhances discharge activity of cortical neurons.

JOURNAL/nrgr/04.03/01300535-202502000-00031/figure1/v/2024-05-28T214302Z/r/image-tiff Transforming growth factor-beta 1 (TGF-ß1) has been extensively studied for its pleiotropic effects on central nervous system diseases. The neuroprotective or neurotoxic effects of TGF-ß1 in specific brain areas may depend on the pathological process and cell types involved. Voltage-gated sodium channels (VGSCs) are essential ion channels for the generation of action potentials in neurons, and are involved in various neuroexcitation-related diseases. However, the effects of TGF-ß1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear. In this study, we investigated the effects of TGF-ß1 on VGSC function and firing properties in primary cortical neurons from mice. We found that TGF-ß1 increased VGSC current density in a dose- and time-dependent manner, which was attributable to the upregulation of Nav1.3 expression. Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase (PD98059), p38 mitogen-activated protein kinase (SB203580), and Jun NH2-terminal kinase 1/2 inhibitor (SP600125). Interestingly, TGF-ß1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons. These findings suggest that TGF-ß1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway, which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions. Thus, this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

A combined analysis of bulk RNA-seq and scRNA-seq was performed to investigate the molecular mechanisms associated with the occurrence of myocardial infarction.

BACKGROUND: Myocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data. METHODS: Publicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis. RESULTS: In scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI. CONCLUSION: MI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.

Bushen Huoxue formula attenuates lipid accumulation evoking excessive autophagy in premature ovarian insufficiency rats and palmitic acid-challenged KGN cells by modulating lipid metabolism.

Introduction: Premature ovarian insufficiency (POI) has affected about 3.7% of women of reproductive age and is a major factor contributing to infertility. Bushen Huoxue formula (BHF), a traditional Chinese medicine prescription, is clinically used to treat POI in China. This study aims to investigate the potential mechanisms of BHF in combating POI using corticosterone-induced rats and palmitic acid (PA)-challenged human ovarian granulosa cells (GCs). Methods: Initially, ultra performance liquid chromatography tandem mass spectrometry was employed to analyze the components of BHF. The pharmacodynamic parameters evaluated included body weight, ovaries index, and serum hormone in rats. Follicle numbers were observed using H&E staining. Additionally, PCNA and TUNEL staining were used to assess GCs proliferation and apoptosis, respectively. Lipid accumulation and ROS levels were examined using Oil Red O and ROS staining. Protein expressions were determined by western blot. To probe mechanisms, cell viability and E2 levels in BHF-treated, PA-stimulated GCs were determined using MTT and ELISA, respectively. Cell apoptosis and ROS levels were assessed using TUNEL and ROS staining. Proteins related to lipid metabolism and autophagy in PA-stimulated GCs were studied using agonists. Results: Our results shown that BHF effectively normalized serum hormone levels, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH). Concurrently, BHF also significantly reduced follicular atresia and promoted cell proliferation while inhibiting apoptosis in POI rats. Furthermore, BHF mitigated ovarian lipid accumulation by modulating lipid metabolism, which included reducing lipid synthesis (expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α), increasing lipid catabolism (expression of adipose triglyceride lipase), and enhancing lipid oxidation (expression of carnitine palmitoyl transferase 1A). Mechanistically, the therapeutic effects of BHF on POI were linked with alleviation of lipid deposition-induced reactive oxygen species (ROS) accumulation and excessive autophagy, corroborating the results in PA-challenged GCs. After treatment with elesclomol (a ROS inducer) and rapamycin (an autophagy inducer) in GCs, the effects of BHF were almost counteracted under model conditions. Conclusion: These findings suggest that BHF alleviates the symptoms of POI by altering lipid metabolism and reducing lipid accumulation-induced ROS and autophagy, offering evidence for BHF's efficacy in treating POI clinically.

Hybrid modality dual-energy imaging aggregating complementary advantages of kV-CT and MV-CBCT: concept proposal and clinical validation.

OBJECTIVE: Megavoltage cone-beam CT (MV-CBCT) is advantageous in metal artifact reduction during Image-Guided Radiotherapy (IGRT), although it is limited by poor soft tissue contrast. This study proposed and evaluated a novel hybrid modality dual-energy (DE) imaging method combining the complementary advantages of kV-CT and MV-CBCT. Approach: The kV-CT and MV-CBCT images were acquired on a planning CT scanner and a Halcyon linear accelerator respectively. After rigid registration, images of basis materials were generated using the iterative decomposition method in the volumetric images. The decomposition accuracy was quantitatively evaluated on a Gammex 1472 phantom. The performance of contrast enhancement and metal artifact reduction in virtual monochromatic images were evaluated on both phantom and patient studies. Main results: Using the proposed method, the mean percentage errors for RED and SPR were 0.90% and 0.81%, outperforming the clinical single-energy mapping method with mean errors of 1.28% and 1.07%, respectively. The contrasts of soft-tissue insets were enhanced by a factor of 2~3 at 40 keV compared to kV-CT. The standard deviation in the metal artifact area was reduced by ~67%, from 42 HU (kV-CT) to 14 HU (150 keV monochromatic). The head and neck patient test showed that the percent error of soft-tissue RED in the metal artifact area was reduced from 18.1% (HU-RED conversion) to less than 1.0% (the proposed method), which was equivalent to the maximum dosimetric difference of 28.7% based on the patient-specific plan. Significance: Without hardware modification or extra imaging dose, the proposed hybrid modality method enabled kV-MV DE imaging, providing improved accuracy of quantitative analysis, soft-tissue contrast and metal artifact suppression for more accurate IGRT. .

Development and validation of a relatively accurate gastric cancer high-risk group screening scoring system in urban residents.

PURPOSE: Our study aimed to develop a relatively accurate gastric cancer (GC) screening score system for urban residents and to validate the screening efficacy. METHODS: The present study included a derivation cohort (n = 3406) and a validation cohort (n = 868) of urban residents. Applying the full-stack engineering intelligent system platform of Hualian Health Big Data of Shandong University, the clinical physical examination data of subjects were collected. Univariate and multivariate analyses were used to identify risk factors for GC, and subsequently, an optimal prediction rule was established to create three distinct scoring systems. RESULTS: In the GC-risk scoring system I, age, plateletocrit (PCT), carcinoembryonic antigen (CEA), glucose, albumin, creatinine were independent risk factors of GC, with scores ranging from 0 to 28 and optimal cut-off was 15.5. The second scoring system consisted of age, PCT, RDW-CV, CEA, glucose, albumin, and creatinine, with scores ranging from 0 to 31. The optimal cut-off point was determined to be 15.5. The scoring system III comprise of age, sex, PCT, RDW CV, CEA, glucose, with scores ranging from 0 to 21 and optimal cut-off was 10.5. All three scoring systems demonstrated excellent discrimination for GC, achieving an AUC of 0.884, 0.89, and 0.876, respectively. In external validation, the AUC values were 0.654, 0.658, and 0.714. Notably, the GC-risk scoring system III exhibited the highest screening efficiency. CONCLUSIONS: Urban residents benefited from the effective and verified GC-risk scoring systems, which demonstrated excellent performance in identifying individuals with an elevated risk of GC.

A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study.

OBJECTIVE: To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory. METHODS: This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared. RESULTS: A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009). CONCLUSION: The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.

Development and validation of a multimodal deep learning framework for vascular cognitive impairment diagnosis.

Cerebrovascular disease (CVD) is the second leading cause of dementia worldwide. The accurate detection of vascular cognitive impairment (VCI) in CVD patients remains an unresolved challenge. We collected the clinical non-imaging data and neuroimaging data from 307 subjects with CVD. Using these data, we developed a multimodal deep learning framework that combined the vision transformer and extreme gradient boosting algorithms. The final hybrid model within the framework included only two neuroimaging features and six clinical features, demonstrating robust performance across both internal and external datasets. Furthermore, the diagnostic performance of our model on a specific dataset was demonstrated to be comparable to that of expert clinicians. Notably, our model can identify the brain regions and clinical features that significantly contribute to the VCI diagnosis, thereby enhancing transparency and interpretability. We developed an accurate and explainable clinical decision support tool to identify the presence of VCI in patients with CVD.

Microsporidia secretory effectors and their roles in pathogenesis.

Microsporidia, a group of unicellular eukaryotic parasites, rely intensely on secretory effectors for successful invasion and proliferation within host cells. This review focuses on the identification, characterization, and functional roles of effectors, including secretory proteins and microRNAs. The adhesion proteins like the Ricin-B-lectin facilitate initial invasion, which binds to the host cell surface. Once inside, microsporidia deploy a range of effectors to modulate host immune responses, such as serpin proteins, and redirect host cell metabolism to meet the parasite's nutritional needs through hexokinase. Some effectors such as microRNAs, alter the host gene expression to create a more favorable intracellular parasitic environment. In conclusion, the secretory effectors of microsporidia play a pivotal role spanning from host cell invasion to intracellular establishment. In the future, more effectors secreted by microsporidia will be studied, which will not only help to elucidate the molecular mechanism of pathogenic manipulation of the host but also help to provide the potential targets for anti-parasitic treatments.

Circular RNAs in human diseases.

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back-splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in-depth examination of circRNAs, focusing first on their involvement in non-neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs' roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

Hydrogen sulfide antagonizes cytokinin to change root system architecture through persulfidation of CKX2 in Arabidopsis.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which has been shown to play an important role in plant growth and development by coupling with various phytohormones. However, the relationship between H2S and cytokinin (CTK) and the mechanisms by which H2S and CTK affect root growth remain poorly understood. Endogenous CTK was analyzed by UHPLC-ESI-MS/MS. Persulfidation of cytokinin oxidase/dehydrogenases (CKXs) was analyzed by mass spectrometry (MS). ckx2/CKX2wild-type (WT), OE CKX2 and ckx2/CKX2Cys(C)62alanine(A) transgenic lines were isolated with the ckx2 background. H2S is linked to CTK content by CKX2, which regulates root system architecture (RSA). Persulfidation at cysteine (Cys)62 residue of CKX2 enhances CKX2 activity, resulting in reduced CTK content. We utilized 35S-LCD/oasa1 transgenic lines to investigate the effect of endogenous H2S on RSA, indicating that H2S reduces the gravitropic set-point angle (GSA), shortens root hairs, and increases the number of lateral roots (LRs). The persulfidation of CKX2Cys62 changes the elongation of cells on the upper and lower flanks of LR elongation zone, confirming that Cys62 of CKX2 is the specificity target of H2S to regulate RSA in vivo. In conclusion, this study demonstrated that H2S negatively regulates CTK content and affects RSA by persulfidation of CKX2Cys62 in Arabidopsis thaliana.

The imaging manifestations of persistent truncus arteriosus in children.

Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.

Coconut milk allergenicity: Insight into reducing the affinity of coconut globulin to immunoglobulin E by atmospheric cold plasma.

Atmospheric cold plasma (ACP) presents a promising method for the sterilization of coconut milk and exhibits a modifying effect on coconut globulin (CG), the primary allergen in coconut milk. This study investigated the potential role of ACP treatment in mitigating the allergenic properties of coconut milk by examining changes in protein structure. ACP treatment induced structural alterations in CG, disrupting binding sites with immunoglobulin E (IgE). Consequently, this led to a reduction in the affinity between CG and IgE, evidenced by a decrease in Ka from 2.17 × 104/M to 0.64 × 104/M, thereby diminishing IgE-mediated allergic reactions. The findings from allergenic and cellular models further corroborated that ACP treatment decreased the allergenicity of CG by 55.18%, while inhibiting degranulation and the release of allergic mediators. This study presents an innovative methodology for producing hypoallergenic coconut milk, thereby expanding the applicability of ACP technology within the food industry.

Clinical value of γ-glutamyl transpeptidase to platelet ratio and triglyceride measurement in the diagnosis of nonalcoholic fatty liver disease: A cross-sectional study.

Objective: In clinical practice, there are few effective biomarkers for identifying non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the diagnostic value of γ-glutamyl transpeptidase to platelet ratio (GPR) combined with triglyceride (TG) in NAFLD. Methods: A total of 14,415 individuals participated in the annual physical examination. Multivariate logistic regression analysis was conducted to investigate the exposure factors associated with NAFLD. Spearman's analysis was performed to assess the correlation among the exposure factors of NAFLD. Furthermore, the diagnostic efficacy of the combination of GPR and TG in NAFLD was analyzed using the receiver operating characteristic curve (ROC). Results: The results of the multivariate logistic regression analysis showed that BMI (OR = 1.619), Systolic Blood Pressure (SBP) (OR = 1.014), Diastolic Blood Pressure (DBP) (OR = 1.028), GPR (OR = 12.809), and TG (OR = 2.936) were all risk factors for NAFLD, while HDL-C (OR = 0.215) was a protective factor. Spearman correlation analysis revealed significant positive correlations between GPR and SBP, DBP, BMI, TG (p < 0.01), but a negative correlation between GPR and HDL-C (p < 0.01). TG was only positively correlated with GPR (p < 0.001). ROC curve analysis demonstrated that the area under the curve (AUC) of GPR combined with TG for diagnosis of NAFLD was 0.855 (95 % CI: 0.819-0.891), sensitivity was 83.45 % and specificity was 73.56 %. Conclusion: This study indicated that high levels of GPR and TG were risk factors for NAFLD and demonstrated good clinical value in diagnosing NAFLD.

The prognostic value of Th17/Treg cell in cervical cancer: a systematic review and meta-analysis.

Background: The prognostic significance of Treg and Th17 cells, as well as their ratio (Th17/Treg), in cervical cancer remains a topic of debate. Our study aimed to clarify their association with patient survival and clinical outcomes in cervical cancer through a comprehensive meta-analysis. Materials and methods: We conducted a comprehensive search in PubMed, Embase, and Web of Science to identify eligible studies. Studies related to cervical cancer and involving Treg cells or Th17 cells were included. For prognostic analysis, we collected Hazard Ratio values of patient survival. For studies focusing on clinical characteristics, we selected mean and standard deviation values for further analysis. This study was registered at PROSPERO (ID:CRD42024546507). Results: Out of the 2949 records initially retrieved, we ultimately included 21 studies in our analysis. High levels of Treg cells were found to be correlated with shorter survival in patients with cervical cancer. Subgroup analysis revealed that the prognostic effect of Treg cells on cervical cancer was not influenced by their source or definition. However, analyses of different survival measures indicated that only Overall Survival showed a correlation with Treg cell levels. Additionally, Treg cells were associated with clinical staging. High-grade Th17 cells were associated with lymphatic metastases and advanced clinical stage. The Th17/Treg ratio was found to be elevated in both cervical intraepithelial neoplasia and cervical cancer patients compared to controls. Discussion: Despite limitations such as heterogeneity among selected studies and inadequate subgroup analyses, our study contributes to a deeper understanding of the significance of Treg cells in the onset and progression of cervical cancer. It also provides valuable insights for future research in immunotherapy. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024546507.

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Therapeutic potential of targeting AKR1C2 in the treatment of prostate cancer.

Prostate cancer development and progression are driven by androgens, and changes in androgen metabolic pathways can lead to prostate cancer progression or remission. AKR1C2 is a member of the aldo-keto reductase superfamily and plays an important role in the metabolism of steroids and prostaglandins. Alterations in the expression and activity of AKR1C2 affect the homeostasis of active androgens, which in turn affects the progression of prostate cancer. AKR1C2 reduces the highly active dihydrotestosterone to the less active 3α-diol in the prostate, resulting in lower androgen levels. Whereas the expression of AKR1C2 is significantly reduced in prostate cancer tissues relative to normal prostate tissues, this results in a weakening of the dihydrotestosterone metabolic inactivation pathway, leading to the retention of dihydrotestosterone in the prostate cancer cells, which promotes the progress of prostate cancer. Given the critical role of AKR1C2 in prostate cancer cells, targeting AKR1C2 for the treatment of prostate cancer may be an effective strategy. It has been demonstrated that curcumin and neem leaf extract effectively inhibit prostate cancer in vitro and in vivo by modulating AKR1C2.

Adeno-associated virus therapies: Pioneering solutions for human genetic diseases.

Adeno-associated virus (AAV) has emerged as a fundamental component in the gene therapy landscape, widely acknowledged for its effectiveness in therapeutic gene delivery. The success of AAV-based therapies, such as Luxturna and Zolgensma, underscores their potential as a leading vector in gene therapy. This article provides an in-depth review of the development and mechanisms of AAV vector-based therapies, offering a comprehensive analysis of the latest clinical trial outcomes in central nervous system (CNS) diseases, ocular conditions, and hemophilia, where AAV therapies have shown promising results. Additionally, we discusse the selection of administration methods and serotypes tailored to specific diseases. Our objective is to showcase the innovative applications and future potential of AAV-based gene therapy, laying the groundwork for continued clinical advancements.

Effect of Structure and Wearing Modes on the Protective Performance of Industrial Safety Helmet.

This study aims to explore the effects of helmet structure designs and wearing modes on the protective performance of safety helmets under the impact of falling objects. Four helmet types (no helmet, V-shaped, dome-shaped, and motorcycle helmets) and five wearing modes (left and right tilt by 5 deg, backward tilt by 15 deg, 0 deg without chin strap, 0 deg with chin strap) were included in this study. The axial impact of a concrete block under various impact velocities was simulated. The results indicate that the energy absorption and shock mitigation effects of the foam cushion are superior to those of the suspension system in traditional industrial safety helmets. The structure of the top of V-shaped helmets is designed to withstand greater impact. Regarding the wearing mode, the helmet strap's deflection angle increases stress in the brain tissue and skull, heightens intracranial pressure, and causes pressure diffusion toward the forehead.